ABC of Interventional Cardiology E-Book

Ever D. Grech

• Herausgeber: John Wiley & Sons
• Kategorie: Fachliteratur
• Serie: ABC Series
• Sprache: Englisch

Seitenzahl: 269

Veröffentlichungsjahr: 2011

Beschreibung

ABC of Interventional Cardiology

This fully updated, new edition of ABC of Interventional Cardiology is an easy-to-read, practical guide for the non-specialist. It presents the complex aspects of interventional cardiology in a clear and concise manner, and explains the different interventions for coronary artery disease, valvular and structural heart disease, and electrophysiology, ordered by clinical setting.

The ABC of Interventional Cardiology covers the core knowledge on techniques and management, and highlights the evidence base. Illustrated in full colour throughout, with new images and graphics, it includes key evidence and guidelines, new drug treatments and devices, with recommendations for further reading and additional resources in each chapter. It is ideal for GPs, hospital doctors, medical students, catheter laboratory staff and cardiology nurses.

About the ABC series
The new ABC series has been thoroughly updated, offering a fresh look, layout and features throughout, helping you to access information and deliver the best patient care. The newly designed books remain an essential reference tool for GPs, GP registrars, junior doctors and those in primary care, designed to address the concerns of general practitioners and provide effective study aids for doctors in training.

Now offering over 70 titles, this extensive series provides you with a quick and dependable reference on a range of topics in all the major specialities. Each book in the new series now offers links to further information and articles, and a new dedicated website provides you with even more support.

The ABC series is the essential and dependable source of up-to-date information for all practitioners and students in general practice.

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Leseprobe

Contents

List of Contributors

Preface

Acknowledgements

List of Abbreviations

List of Trial Abbreviations

1 Modifying Risk Factors to Improve Prognosis

Impact of risk factors

How to assess cardiovascular risk

Effects of drug treatments

Effects of coronary artery revascularisation

Conclusion

Further reading

2 Pathophysiology and Investigation of Coronary Artery Disease

Pathophysiology

Investigations

Non-invasive investigations

Invasive investigations

Further reading

3 Percutaneous Coronary Intervention (I): History and Development

Classification

History of myocardial revascularisation

Developments in percutaneous coronary intervention

Drills, cutters and lasers

Intracoronary stents

Further reading

4 Percutaneous Coronary Intervention (II): The Procedure

Clinical risk assessment

Preparation for intervention

The procedure

Recovery

Complications and sequelae

Restenosis within a stent

Drug-eluting stents

Late stent thrombosis

Perioperative care of patients with stents

In-stent restenosis

Occupation and driving

Further reading

5 Chronic Stable Angina: Treatment Options

Treatment strategies

Comparative studies of revascularisation strategies

Left main stem disease

Refractory coronary artery disease

Further reading

6 Acute Coronary Syndrome: Unstable Angina and Non-ST Segment Elevation Myocardial Infarction

Pathogenesis

Epidemiology

Diagnosis

Management

Conclusion

Further reading

7 Acute Coronary Syndrome: ST Segment Elevation Myocardial Infarction

Recanalisation

Pros and cons of primary PCI

Primary PCI and coronary stents

Glycoprotein IIb/IIIa inhibitors and other antiplatelet agents

Adjunctive mechanical devices

Future of primary PCI

Further reading

8 Percutaneous Coronary Intervention: Cardiogenic Shock

Effects of cardiogenic shock

Time course of cardiogenic shock

Differential diagnosis

Management

Further reading

9 Interventional Pharmacotherapy

Coronary artery thrombosis

Bleeding

Anticoagulant drugs

Antiplatelet drugs

Current use of glycoprotein IIb/IIIa receptor antagonists

Restenosis

The future

Further reading

10 Non-coronary Percutaneous Intervention

Balloon mitral valvuloplasty

Percutaneous mitral valve repair

Transcatheter aortic valve implantation (TAVI)

Ethanol septal ablation

Septal defect closure

Further reading

11 New Developments in Percutaneous Coronary Intervention

Introduction

The changing patient population

Chronic total occlusions

Bifurcation lesions

Diseased vein grafts

Better imaging

Better guidewires

Better balloons

Better catheters

Better stent platforms

Better adjunct therapy

Further reading

12 Percutaneous Interventional Electrophysiology

Intracardiac electrophysiological studies

Atrioventricular conduction

Retrograde ventriculoatrial conduction

Supraventricular tachycardia

Atrial flutter

Atrial fibrillation (AF)

Ventricular tachycardia

Conclusion

Further reading

13 Implantable Devices for Treating Tachyarrhythmias

Mechanisms of pacing termination for ventricular tachycardias

Indications for defibrillator use

Devices for heart failure

Future developments

Further reading

14 Pacemakers for Bradycardia

Introduction

Technological advances

Battery technology

Lead technology

Rate response

Pacemaker memory

Clinical indications

Which type of pacemaker?

Pacemaker terminology

Which pacemaker for which patient?

Complications

Pacing malfunction

Living with a pacemaker

Pacemaker controversies

The present and future

Conclusion

Further reading

15 Heart Failure, Dys-synchrony and Resynchronisation Therapy

Heart failure

Dys-synchrony

Guidelines from National Institute of Health and Clinical Excellence (NICE)

Further reading

16 Interventional Paediatric Cardiology

Basic techniques

Dilatations

Occlusions

Percutaneous intervention and surgery

Further reading

Index

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Index

This edition first published 2011, © 2011 by Ever D. Grech

Previous edition: 2003

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Library of Congress Cataloging-in-Publication Data

ABC of interventional cardiology / Ever D. Grech. – 2nd ed.

p.; cm.

Includes bibliographical references and index.

ISBN 978-1-4051-7067-3 (pbk.: alk. paper)

1. Heart – Diseases – Treatment. 2. Coronary heart disease – Surgery. I. Grech, Ever D.

[DNLM: 1. Cardiovascular Diseases – therapy. WG 120]

RC683.8.A33 2010

616.1′2-dc22

2010039150

ISBN: 978-1-4051-7067-3

List of Contributors

Abdallah Al-Mohammad

Consultant Cardiologist, South Yorkshire Cardiothoracic Centre, Northern General Hospital, Sheffield, UK

Kevin S. Channer

Professor of Cardiovascular Medicine, Royal Hallamshire Hospital, Sheffield, UK

Ever D. Grech

Consultant Cardiologist, South Yorkshire Cardiothoracic Centre, Northern General Hospital, Sheffield, UK

Julian Gunn

Senior Lecturer and Honorary Consultant Cardiologist, University of Sheffield, Sheffield, UK

Gerald C. Kaye

Consultant Cardiac Interventional Electrophysiologist, Princess Alexandra Hospital, Woolloongabba, Brisbane, QLD, Australia

Damien Kenny

Specialist Registrar in Paediatric Cardiology, Bristol Royal Hospital for Children, Bristol, UK

Laurence O’Toole

Consultant Cardiologist, South Yorkshire Cardiothoracic Centre, Northern General Hospital, Sheffield, UK

Jonathan Sahu

Consultant Cardiologist, South Yorkshire Cardiothoracic Centre, Northern General Hospital, Sheffield, UK

Robert F. Storey

Reader and Honorary Consultant Cardiologist, University of Sheffield, Sheffield, UK

Kevin P. Walsh

Consultant Paediatric Cardiologist, Our Lady’s Hospital for Sick Children, Dublin, UK

Preface

It is only 33 years since the first percutaneous transluminal coronary angioplasty (PTCA) was carried out by the pioneering Swiss radiologist Andreas Greuntzig in Zurich, heralding the dawn of interventional cardiology. In this short time, interventional cardiology has overcome many limitations and undergone major evolutionary changes – most notably the development of the intracoronary stent and more explicitly the drug-eluting stent. Across the world, many thousands of patients now safely undergo percutaneous coronary intervention everyday and the numbers continue to grow. In many countries, the numbers far exceed surgical bypass operations.

Although at first, PTCA was indicated only as treatment for chronic stable angina caused by a discrete, easily accessible lesion in a single coronary artery, this has now progressed enormously to encompass complex multi-lesion and multi-vessel disease. Moreover, percutaneous coronary intervention has now become widely used in the management of acute coronary syndromes (which principally include ‘heart attacks’) with definite benefits in terms of morbidity and mortality. The effectiveness and safety of these procedures has undoubtedly been enhanced by the adjunctive use of new anti-platelet and anti-thrombotic agents, and newer drugs are being evaluated. As drug-eluting stents address the Achilles’ heel of angioplasty and stents – restenosis – the huge increase in percutaneous coronary procedures seen over recent years is likely to continue.

As the indications increase and more patients are treated, so inevitably do the demands on healthcare budgets. Although percutaneous intervention is expensive, this burden must be weighed against bypass surgery which is significantly more costly and multi-drug therapy which would be required over many years.

Although percutaneous coronary intervention has held centre stage in cardiology, major in-roads have also been made in non-coronary areas. Transcatheter valvular treatments – including actual new valve implantation, closure devices and ethanol septal ablation – have become effective and safe alternatives to surgery, as have paediatric interventional procedures. A greater understanding of cardiac electrophysiology and heart failure has led to important advances in the treatment of arrhythmias and resynchronisation therapy. Pacemakers, implantable cardioverter defibrillators (ICD) and cardiac resynchronisation therapy (CRT) are benefiting ever larger numbers of patients both in terms of life quality and mortality.

Where are we heading? This is perhaps the biggest question in the minds of many interventional cardiologists. New ideas and technology generated by industry, coupled with high levels of expertise, are fuelling advances in almost all areas of interventional cardiology. The next decade promises many new (and possibly unexpected) developments in this exciting and restless field of medicine.

In writing this book, I have endeavoured to present broad (and sometimes complex) aspects of interventional cardiology in a clear, concise and balanced manner. To this end, I have concentrated on an easy-to-read style of text, avoiding jargon and exhaustive detail where possible and supplemented with many images and graphics.

Ever D. Grech

Sheffield

Acknowledgements

I have many people to thank for their help in developing and producing this book. I am very grateful to my co-authors who have all willingly contributed their time and expertise. I would also like to recognise the positive efforts and invaluable assistance of the editors and publishers at Wiley-Blackwell. These include Laura Quigley, Adam Gilbert, Carla Hodge and Karen Moore. My thanks also to Dhanya Ramesh at Laserwords.

Finally, my enduring gratitude goes to my wife Lisa and our children Alexander and Frances for their unfailing encouragement, patience and love.

List of Abbreviations

CTOChronic total occlusionHRTHormone replacement therapyIVUSIntravascular ultrasoundLADLeft anterior descending (artery)LCxLeft circumflex (artery)Non-STEMI Non-STsegment elevation myocardial infarctionPCIPercutaneous coronary interventionRCARight coronary arterySTEMI STsegment elevation myocardial infarction

List of Trial Abbreviations

ACEAbciximab and Carbostent EvaluationADMIRALAbciximab before Direct Angioplasty and Stenting in Myocardial Infarction Regarding Acute and Long-Term Follow-upASSENT-4Assessment of the Safety and Efficacy of a New Treatment Strategy for Acute Myocardial InfarctionBARIBypass Angioplasty Revascularisation InvestigationCADILLACControlled Abciximab and Device Investigation to Lower Late Angioplasty ComplicationsCAPITAL-AMICombined Angioplasty and Pharmacological Intervention Versus Thrombolytics Alone in Acute Myocardial InfarctionCAPTURE C7E3Antiplatelet Therapy in Unstable Refractory AnginaCARDiaCoronary Artery Revascularisation in DiabetesCARE-HFCardiac Resynchronization – Heart FailureCARESS-in-AMICombined Abciximab REteplase Stent Study in Acute Myocardial InfarctionCHAMPIONCangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet InhibitionCHARISMAClopidogrel for High Atherothrombotic Risk and Ischemic Stabilization Management and AvoidanceCLARITYClopidogrel as Adjunctive Reperfusion TherapyCOMMITClopidogrel and Metoprolol in Myocardial Infarction TrialCOMPANIONComparison of Medical Therapy, Pacing, and Defibrillation in Chronic Heart FailureCOURAGEClinical Outcomes Utilising Revascularisation and Aggressive Drug EvaluationCREDOClopidogrel for the Reduction of Events during ObservationCUREClopidogrel in Unstable Angina to Prevent Recurrent EventsECSGEuropean Cooperative Study GroupEPICEvaluation of C7E3 for Prevention of Ischemic ComplicationsEPILOGEvaluation in PICA to Improve Long-Term Outcome with Abciximab Glycoprotein IIb/IIIa BlockadeEPISTENTEvaluation of Platelet IIb/IIIa Inhibitor for StentingESPRITEnhanced Suppression of the Platelet Glycoprotein IIb/IIIa Receptor Using Integrilin TherapyEUROPAEuropean Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery DiseaseEVERESTEndovascular Valve Edge-to-Edge Repair StudyFAME FFRVersus Angiography for Multivessel EvaluationFINESSEFacilitated Intervention with Enhanced Reperfusion Speed to Stop EventsFREEDOMFuture Revascularisation Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel DiseaseFRISC IIFast Revascularisation during Instability in Coronary Artery DiseaseGISSIGruppo Italiano per to Studio della Sopravvivenza nell’infarto miocardicoGUSTOGlobal Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary ArteriesGUSTOIV ACS Global Use of Strategies to Open Occluded Arteries IV in Acute Coronary SyndromeHOPEHeart Outcomes Prevention EvaluationHORIZONS-AMIHarmonizing Outcomes with Revascularization and Stents in Acute Myocardial InfarctionICTUSInvasive Versus Conservative Treatment in Unstable Coronary Syndromes InvestigatorsIMPACT IIIntegrilin to Minimize Platelet Aggregation and Coronary ThrombosisISAR-COOLIntracoronary Stenting with Antithrombotic Regimen Cooling OffISAR-REACT 2Intracoronary Stenting and Antithrombotic Regimen – Rapid Early Action for Coronary Treatment 3ISIS-2Second International Study of Infarct SurvivalJUPITERJustification for the Use of Statins in Prevention: an Intervention Trial Evaluating RosuvastatinMADIT I and IIMulticenter Automatic Defibrillator Implantation Trials. The Use of Defibrillators in Primary PreventionMISTMigraine Intervention with Starflex TechnologyMUSTTMulticenter Unsustained Tachycardia TrialOn-TIME 2Ongoing Tirofiban in Myocardial Infarction EvaluationPARAGONPlatelet IIb/IIIa Antagonism for the Reduction of Acute Coronary Syndrome Events in the Global Organization NetworkPEACEPrevention of Events with Angiotensin-Converting Enzyme InhibitionPLATOPlatelet Inhibition and Patient OutcomesPRISMPlatelet Receptor Inhibition in Ischemic Syndrome ManagementPRISM-PLUSPlatelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and SymptomsPROSPECTPredictors of Response to Cardiac Resynchronization TherapyPURSUITPlatelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin TherapyRAPPORTReopro and Primary PTCA Organization and Randomized TrialRAVELRandomised Study with the Sirolimus-Eluting Velocity Balloon-Expandable Stent in the Treatment of Patients with De Novo Native Coronary Artery LesionsRESTORERandomized Efficacy Study of Tirofiban for Outcomes and RestenosisRITA 3Randomised Intervention Treatment of AnginaSCD-HeftSudden Cardiac Death in Patients with Heart FailureSHOCKShould We Emergently Revascularize Occluded Coronaries for Cardiogenic ShockSIRIUSSirolimus-Coated Velocity Stent in Treatment of Patients with De Novo Coronary Artery Lesions TrialStent-PAMIStent Primary Angioplasty in Myocardial InfarctionSYNTAXSynergy between PCI with Taxus and Cardiac SurgeryTACTICS-TIMI 18Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy– Thrombolysis in Myocardial Infarction TAMI Thrombolysis and Angioplasty in Myocardial InfarctionTIMIIIIBThrombolysis in Myocardial Infarction IIIBTRANSFER-AMITrial of Routine Angioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial InfarctionTRITON-TIMI 38Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel – Thrombolysis in Myocardial InfarctionTRUCSTreatment of Refractory Unstable Angina in Geographically Isolated Areas without Cardiac SurgeryVANQWISHVeterans Affairs Non-Q-Wave Infarction Strategies in HospitalVINOValue of First Day Coronary Angiography/Angioplasty in Evolving Non-ST Segment Elevation Myocardial InfarctionWHO MONICAWorld Health Organisation: Monitoring Trends and Determinants in Cardiovascular Disease

CHAPTER 1

Modifying Risk Factors to Improve Prognosis

Kevin S. Channer1 and Ever D. Grech2

1Royal Hallamshire Hospital, Sheffield, UK

2South Yorkshire Cardiothoracic Centre, Northern General Hospital, Sheffield, UK

OVERVIEW

Certain personal characteristics and lifestyles point to increased likelihood of coronary heart disease and are called risk factorsThe three principal modifiable risk factors are smoking, hypercholesterolaemia and hypertension. Other modifiable factors linked to lifestyle include a saturated-fat-rich diet, obesity and physical inactivityPrevention strategies (primary or secondary prevention) aim to reduce the risk of developing or retard the progression of atheroma, to stabilise plaques and to reduce the risk of their erosion or rupture. These measures can collectively reduce the risk of future cardiovascular events (mortality, myocardial infarction and strokes) by as much as 75–80%Percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) revascularisation is not a cure for coronary heart disease and they are predominantly carried out to improve symptoms. They may have little or no prognostic impact in chronic stable angina. However, CABG and PCI confer significant short- and long-term mortality benefit in acute coronary syndromes and, in particular, primary PCI for acute ST segment elevation myocardial infarction

In affluent societies, coronary artery disease causes severe disability and more deaths than any other disease including cancer. It manifests itself as silent ischaemia, angina, unstable angina, myocardial infarction, arrhythmias, heart failure and sudden death. Although this is the result of atheromatous plaque formation and its effect, the actual cause of this process is not known. However, predictive variables – known as risk factors –have been identified which increase the chance of its early development. Risk factors can be classified as modifiable and non-modifiable (Table 1.1).

It is clearly not possible to prevent the increased risk associated with ageing, a positive family history or male gender. However, there are many factors which can be usefully ameliorated by interventions. Moreover, there are some aspects of lifestyle that have been shown to reduce the risk of an acute myocardial infarction.

Table 1.1 Risk factors for the development of premature ischaemic heart disease and acute myocardial infarction.

Uncertain risk factors include: hypertriglyceridaemia, lipoprotien (a), microalbuminuria, uric acid, renin, fibrinogen, C-reactive protien and hyperhomocyteinaemia. *From Steeds. RR, Relative risk.

†From INTERHEART case-control study. Yusuf S et al. Lancet 2004;364: 937–52.

‡For current and former smokers.

RR for AMI: Relative risk for acute myocardial infarction. PAR for AMI(%): Population attributable risk for acute myocardial infarction. Notes: These 9 risk factors accounted for 90% of the population attributable risk in men and 94% in women. Psychosocial factors included depression, stress at work or at home, moderate/severe financial stress, one or more recent life events, low control score. The control population was drawn from hospital in-patients with non-cardiac conditions (58%) and community-based hospital visitors (36%). A minority were WHO MONICA controls (3%) and unknown (3%).

Risk factors are not simply additive but may be synergistically cumulative. Data from epidemiological surveys have shown for some time that combinations of risk factors generate exponential risks (Figures 1.1 and 1.2). This applies to both men and women. Risk factors are not static but increase with age – this may partly explain the independent effect of age. Blood pressure increases normally with age, so whatever definition is used for hypertension, the frequency of this condition will increase with age. Cholesterol and triglycerides increase with age as do insulin resistance and body mass index.

Figure 1.1 The adverse effect of single and combined risk factors on the risk of acute myocardial infarction. Smk, smoking; DM, diabetes mellitus; HTN, hypertension; ApoB/A1, lipid abnormalities; Obes, obesity; PS, psychosocial factors; RFs, risk factors. From INTERHEART case-control study. Yusuf S et al. Lancet 2004;364:937–52.

Figure 1.2 The beneficial effect of single and combined risk factors on the risk of acute myocardial infarction. No smk, no smoking; Fr/Veg, daily 5 fresh fruits/vegetables; Exer, regular exercise; Alc, regular alcohol. From INTERHEART case-control study. Yusuf S et al. Lancet 2004;364:937–52.

Impact of risk factors

Smoking

Smoking confers a fivefold relative risk for acute myocardial infarction and cardiovascular death. By comparison, stopping smoking has an almost immediate effect on reducing the cardiovascular risk by about 50%. Ex-smokers still have a higher risk than lifelong non-smokers. In one study, the survival rate of patients who stopped smoking after an acute myocardial infarction at 8 years of follow-up was about 75% compared with 60% for patients who continued to smoke. Similarly reinfarction is about twice as common in smokers than in those who stop smoking after a first infarction. At 8 years of follow-up, reinfarction was about 38% in smokers compared with 22% in quitters. Overall smoking increases mortality by about 2.5 times and reduces absolute survival by, on average, 10 years.

Hyperlipidaemia

High blood cholesterol is associated with an increased cardiovascular risk. However, as a single risk factor it is relatively weak – it becomes more important when associated with smoking, hypertension and diabetes. There is also an important interaction with age. In men, there is a doubling of risk from serum cholesterol in the lowest population quintile (<200 mg/dl; 5.2 mmol/l) to the highest (>260mg/dl; >6.7mmol/l).

Hypertension

Both diastolic and systolic hypertension have been shown to be risk factors for myocardial infarction and cardiovascular death. The relative risk of persistently elevated blood pressure of > 160 mmHg systolic is 4 times the risk compared with systolic blood pressure of < 120 mmHg.

The relative risk of persistently elevated diastolic blood pressure > 100 mmHg is 3 times higher when compared with a diastolic pressure of <80mmHg. Research data have shown that reduction in diastolic pressure of 5–6 mmHg and systolic pressure of 10–14 mmHg over 5 years with drug therapy does reduce cardiac mortality and non-fatal myocardial infarction in elderly people by about 20%, and in younger people by about 14%. Data from the longitudinal epidemiological study in Framingham showed that left ventricular hypertrophy diagnosed by echocardiography is associated with a twofold increased risk in death in women and a 1.5-fold increased risk in men over a 4-year period.

Diabetes mellitus

This is a major risk factor for premature vascular disease, stroke, myocardial infarction and death. Diabetes increases the risk of developing coronary heart disease by 1.5 times at age 40–49 and by 1.7 times at age 50–59 in men and by 3.7 times at age 40–49, and 2.4 times at age 50–59 in women. There are data that show that diabetic control is important for cardiovascular risk, with correlations between cardiovascular events, ischaemic heart disease and death rate and glycosylated haemoglobin. Much more effective risk reduction is associated with aggressive treatment of the commonly associated hypertension, lipid abnormalities and obesity in the diabetic patient.

Obesity

Obesity has been increasing in epidemic proportions and confers a prognostic disadvantage. Those with body mass index (weight/ht2) of 25–29 kg/m2 are considered to be overweight and those >32 are classified as obese. The latter have a twofold relative increase in mortality from all causes and a threefold increase in cardiovascular death. One study showed that a high body mass index was associated with an increase risk of death per se, especially when it was present in young people aged 30–44 years. More recent evidence suggests that waist circumference is an important independent risk factor as truncal or visceral obesity appears to be more atherogenic. An expanded waist circumference is a necessary criterion for the diagnosis of the metabolic syndrome, in addition to at least two of the other four criteria (Table 1.2).

Table 1.2 International Diabetes Federation definition of metabolic syndrome – focus on waist circumference.

Abdominal obesity plus at least two of the following:>94 cm male, >80 cm femaleElevated triglycerides≥1.7 mmol/lReduced HDL-cholesterol<1.0 mmol/l male, 1.3 mmol/l femaleRaised blood pressure>130/80 mmHgRaised fasting plasma glucose≥5.6 mmol/l

HDL, High-density lipoprotein.

Despite the presence of the obesity paradox – overweight and obese patients with established cardiovascular disease seem to have a more favourable prognosis than leaner patients – there is data to support purposeful weight reduction in the prevention and treatment of cardiovascular diseases. Furthermore, interventional trials involving bariatric surgery for severe obesity have shown that significant weight reduction resulted in significantly reduced mortality.

Physical activity and fitness

There is a close inverse relationship between cardiorespiratory fitness and cardiac outcomes such as coronary disease and death. This can be readily assessed by exercise tolerance testing. Patients with a low level of cardiorespiratory fitness have a 70% higher risk for all-cause mortality and a 56% higher risk for coronary or cardiovascular events compared with those with a high level of fitness. Those with intermediate levels of fitness have a 40% higher mortality risk and a 47% higher coronary or cardiovascular event rate than those with higher fitness. Following acute myocardial infarction or coronary artery bypass graft (CABG), cardiac rehabilitation programmes that promote exercise and weight loss can improve cardiometabolic risk profiles of patients.

Gender

Men have twice the cardiovascular mortality as women at all ages and in all parts of the world. This was thought to be related to the beneficial effect of female sexhormones, especially oestrogens, as the cardiovascular risk in women increases after the menopause. However, two large randomised controlled trials showed that hormone replacement therapy (HRT) did not reduce the cardiovascular risk in women; rather, the thrombotic effects of oestrogens precipitated fatal and non-fatal cardiovascular events, especially in the early years of treatment. Women appear to possess differently weighted risk factors than men for reasons that are unclear.

More recent data have shown strong associations of accelerated atherosclerosis with low levels of testosterone in men followed up for 4–8 years. Low testosterone level in men has been shown to be linked with increased mortality. Male HRT has not yet been shown to reduce cardiovascular risk, although results from animal studies are encouraging.

Psychosocial factors

Some psychosocial factors double the risk of developing cardiovascular disease. Social class has an important effect on mortality from heart disease with people in low-income groups having an excess mortality compared with high-income earners. This is not simply related to deprivation. Within the same working cohort (e.g. Whitehall civil servants), cardiovascular events and mortality were found to be 2–3 times higher in those workers with low socioeconomic status compared with those with high socioeconomic status. In fact, there is little relationship between actual average income and life expectancy. It is not just a matter of money. Mortality is 2–3 times higher in people with poor social links than in those with good social support networks. The reasons are unclear but they are not explained by differences in other known risk factors such as smoking.

Depression

Depression carries an adverse prognosis, especially in association with coronary artery disease and is associated with an eightfold increase in cardiovascular death. Patients with depression have a fivefold increased mortality after acute myocardial infarction. There are no data to suggest that treatment of depression with any specific therapy reverses the excess mortality. Depression also influences the outcome after coronary artery bypass surgery. After controlling for age, sex, number of grafts, diabetes, smoking, left ventricular ejection fraction and previous myocardial infarction, moderate or severe depression at the time of surgery increased the risk of death by 2.4 times, and mild to moderate depression that persisted for 6 months conferred a 2.2 times increased risk of death, during a 5-year follow-up period.

How to assess cardiovascular risk

Cardiovascular risk stratification is carried out through clinical history, physical examination and serum biomarkers. Following extensive validation, tools such as the Framingham or Reynolds risk scores have been adopted in clinical practice by most primary care practitioners. These scores can identify patients with established risk factors who are at greater risk and would most likely benefit from primary prevention. There are also a number of risk estimates that can be provided electronically from the internet (www.riskscore.org.uk;www.bhsoc.org) that have used large populations on which to base risk assessment. They may have some limitations as they are spot estimates that are critically dependent on age as well as actual measurements of blood pressure and cholesterol – which can fluctuate.

More recently, non-invasive imaging of coronary plaque using cardiac magnetic resonance (CMR) and calcification with measurement of coronary calcium using multislice computed tomography (MSCT) scanning have also been used to identify higher risk populations. However, it is as yet uncertain whether treatment modification in this group will result in improved clinical outcome.

Effects of drug treatments

There are two distinct groups of patients who are treated with drug therapy. The first includes those with risk factors for the development of premature vascular disease who do not as yet have overt disease, and is categorised as primary prevention. The second includes those patients who have overt cardiovascular disease, such as previous myocardial infarction, peripheral vascular disease and stroke, and is categorised as secondary prevention. The physician must weigh up the risks and benefits of treatment in each individual patient. For example, in patients with overt vascular disease the threshold for drug treatment is much lower because there is a higher benefit to risk ratio from the known drug treatment. In those patients who are at risk but who do not yet have overt disease, the risks may outweigh the benefits especially if the overall likelihood of a cardiovascular event is small. Age has a large effect here as the risk of developing vascular disease increases exponentially over the age of 65. Moreover, the absolute risk of an event increases with age, so decisions about the appropriateness of primary prevention need to be reviewed on a regular basis as the patient ages. There are risk calculators available to help the physician make treatment decisions.

Aspirin

Aspirin reduces platelet activation by the inhibition of cyclooxygenase-1 (COX-1) enzyme in platelets, blocking the synthesis of prostaglandin G2/H2 and thromboxane A2. It is the most commonly prescribed drug for the prevention of atherothrombotic events. Its use in patients early after acute myocardial infarction is associated with a reduction in mortality of about 25% (ISIS-2 study). When used in patients with chronic stable angina, there is some evidence that myocardial infarction and sudden death as a combined end point is reduced by about 30%. The benefit is seen almost immediately on starting the drug. However, the benefit of aspirin is to postpone events and not to prevent them. By comparing the event rate in patients taking aspirin and placebo, it is possible to estimate the delay in events conferred by the drug. The average benefit is a delay in event rate of maximum 24 months with aspirin. Aspirin for primary prevention remains controversial as the relatively small benefit is offset by gastrointestinal problems such as bleeding.

Clopidogrel

A thienopyridine derivative, clopidogrel prevents adenosine diphosphate (ADP)-mediated activation of platelets, thereby blocking activation of the glycoprotein IIb/IIIa complex.

In terms of primary prevention, clopidogrel offers no benefit over aspirin and may even cause harm. In the CHARISMA study, a long-term trial of aspirin combined with clopidogrel versus aspirin alone, there was no significant benefit over aspirin alone and a suggestion of harm in those patients who had risk factors for cardiovascular disease compared with those who had overt disease. However, in patients with overt vascular disease, the drug has been shown to reduce cardiovascular events by about the same degree as aspirin.

In the setting of acute non-ST segment elevation acute coronary syndome, patients had fewer ischaemic end points when treated with the combination of clopidogrel and aspirin compared with aspirin alone, irrespective of whether percutaneous coronary intervention (PCI) was performed or not (CURE study). In the setting of acute ST segment myocardial infarction treated with aspirin and thrombolytic therapy, the addition of clopidogrel for 1 month conferred a small but significant benefit at 1 month (CLARITY and COMMIT studies).

Cholesterol-lowering drugs

Statins (3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) inhibitors) have been shown to reduce all-cause mortality and cardiovascular events (acute myocardial infarction, angina, stroke) in both primary and secondary prevention of cardiovascular disease (Figure 1.3).

In a meta-analysis involving over 70,000 patients without established cardiovascular disease but with cardiovascular risk factors, statin therapy was associated with a significant risk reduction in all-cause mortality of 12%, in major coronary events of 30% and in major cerebrovascular events of 19%. Moreover, statin use was not associated with an increased risk of cancer.

Statins may have additional antiplatelet and anti-inflammatory benefits. Recently, the JUPITER study showed that rosuvastatin significantly reduced the incidence of major cardiovascular events in apparently healthy people without hyperlipidaemia, but elevated high-sensitivity C-reactive protein (hs-CRP). The proposal that an elevated hs-CRP may be a risk marker or risk factor remains uncertain. Statins have no proven benefit in patients with heart failure.